Functioning of the hypophyseal-adrenocortical system in rats selected for the sensitivity threshold to the electric current

Although behavioral and neuropsychological data regarding the existence of images for odors are inconclusive, reconsideration of earlier EEG work provides reasonably clear evidence for an inner nose. However, further EEG studies and neuroimaging data seem essential for conclusive demonstration of an inner nose.     

Vigabatrin-induced lesions in the rat brain demonstrated by quantitative magnetic resonance imaging

Previous research has indicated that individual foods or beverages are ingested independently and do not produce adjustments to the intake of other constituents in the diet (de Castro, 1993; Wilson, 1991). In order to eliminate time of day as a potential contaminant, the present study investigated the accommodation of foods and beverages into the amount ingested at large evening meals only. Adults (n = 601) were paid to maintain detailed diaries of the timings, quantities and preparation techniques of everything they ingested for seven consecutive days. With the exceptions of soup, beef and chicken, 12 out of 15 types of drinks or foods were found to add to the total calories ingested in evening meals without displacing calories ingested in other forms, while ingestion of non-caloric diet sodas was not associated with differences in intake. The fat and protein, but not carbohydrate, contents of the items correlated with a measure of the satiating properties of the particular food or beverage, namely the correlation between the amount ingested of the particular type and the amounts of other nutrients ingested in the meal. The results confirm that intake at a meal is quite elastic and can be significantly influenced by the presence or absence of particular components of the meal and their constituents.     

Structure-activity studies of the regulatory interaction of the 10 kilodalton C-terminal fragment of caldesmon with actin and the effect of mutation of caldesmon residues 691-696

We have used isotope-edited nuclear magnetic resonance spectroscopy, binding studies, and ATPase activity assays to investigate the interaction with F-actin of the 10 kDa C-terminal 658C fragment of chicken gizzard caldesmon and two site-directed mutants of this fragment. Simultaneous dual-sited contacts with F-actin are observed for the segments of the 658C sequence flanking tryptophan residues 692 and 722. Competition experiments showed that both 658C contacts with actin are displaced by substoichiometric concentrations of the short inhibitory region of troponin-I indicative of different binding sites on actin for these regions of troponin-I and caldesmon. Substitution of caldesmon serine-702 by aspartic acid within the spacer region linking the two actin contacts of 658C led to weaker binding but with retention of equivalent affinity for each interaction site. Differential binding affinity of the two sites was achieved by replacement of the sequence Glu691-Trp-Leu-Thr-Lys-Thr696 by Pro-Gly-His-Tyr-Asn-Asn. Consistent with these data, the concentration of this Cg1 mutant required to achieve 50% inhibition of actin-tropomyosin-activated myosin ATPase was 4-fold greater than found for the 658C fragment. Although calmodulin binding to Cg1 was observed, calmodulin proved ineffective in relieving the inhibition induced by the binding of this mutant to actin. These results are discussed in light of the actin contacts which are involved in the inhibitory activity possessed by different regions of the C-terminus of caldesmon.     

Inhibition of fatty acid synthesis induces programmed cell death in human breast cancer cells

One of the key limiting factors in the treatment of advanced stage human epithelial malignancies is the lack of new, selective molecular targets for antineoplastic therapy. A substantial subset of human breast, ovarian, endometrial, colorectal, and prostatic cancers express elevated levels of fatty acid synthase, the major enzyme required for endogenous fatty acid biosynthesis, and carcinoma lines are growth inhibited by cerulenin, a noncompetitive inhibitor of fatty acid synthase. We have shown previously that the difference in fatty acid biosynthesis between cancer and normal cells is an exploitable target for metabolic inhibitors in the in vitro setting and in vivo in a human ovarian carcinoma xenograft in nude mice. Here, we report that cerulenin treatment of human breast cancer cells inhibits fatty acid synthesis within 6 h after exposure, that loss of clonogenic capacity occurs within the same interval, and that DNA fragmentation and morphological changes characteristic of apoptosis ensue.     

Acute polyneuropathy after high dose cytosine arabinoside in patients with leukemia

BACKGROUND: Peripheral nerve toxicity has been reported but is not a commonly recognized complication of high dose cytosine arabinoside (HDAC) therapy. This study was undertaken to estimate the prevalence and describe the clinical spectrum of acute polyneuropathy associated with HDAC therapy for leukemia. METHODS: Records of 153 acute leukemia patients who received 194 courses of HDAC at the City of Hope were reviewed for evidence of severe peripheral neuropathy with onset 2-3 weeks after HDAC therapy. RESULTS: Two patients were identified who developed motor disability 2-3 weeks after HDAC therapy, and the disability progressed in a monophasic course to quadriparesis. There was neurophysiologic evidence of peripheral nerve demyelination with slowed nerve conduction velocities and conduction block. One patient who was autopsied had demyelination identified in luxol-fast blue sections of peripheral nerve (with Bielschowsky-stained sections showing intact peripheral nerve axons). There were foamy macrophages in the peripheral nerve but no chronic inflammatory cells. For comparison, data from these two patients were combined with those from four published case reports of polyneuropathy associated with HDAC therapy. Quadriparesis occurred in five of six cases with the need for ventilatory support in four. Cerebrospinal fluid protein was elevated in five of six cases. Etiologic evidence incriminating HDAC included simultaneous cerebellar signs in two of six cases and a narrow interval of clinical onset after HDAC therapy. CONCLUSIONS: Demyelinating polyneuropathy occurs in approximately 1% of HDAC courses and produces severe motor disability. HDAC immunosuppression could trigger an immune-mediated neuropathy; alternatively, a direct neurotoxic effect of HDAC on Schwann cells is also an etiologic possibility.     

In vitro system for differentiating pluripotent neural crest cells into smooth muscle cells

The change in vascular smooth muscle cells (SMC) from a differentiated to a dedifferentiated state is the critical phenotypic response that promotes occlusive arteriosclerotic disease. Despite its importance, research into molecular mechanisms regulating smooth muscle differentiation has been hindered by the lack of an in vitro cell differentiation system. We identified culture conditions that promote efficient differentiation of Monc-1 pluripotent neural crest cells into SMC. Exclusive Monc-1 to SMC differentiation was indicated by cellular morphology and time-dependent induction of the SMC markers smooth muscle alpha-actin, smooth muscle myosin heavy chain, calponin, SM22alpha, and APEG-1. The activity of the SM22alpha promoter was low in Monc-1 cells. Differentiation of these cells into SMC caused a 20-30-fold increase in the activity of the wild-type SM22alpha promoter and that of a hybrid promoter containing three copies of the CArG element. By gel mobility shift analysis, we identified new DNA-protein complexes in nuclear extracts prepared from differentiated Monc-1 cells. One of the new complexes contained serum response factor. This Monc-1 to SMC model should facilitate the identification of nodal regulators of smooth muscle development and differentiation.     

Germ cell cancer and disorders of spermatogenesis: an environmental connection?

Why is there a small peak of germ cell tumours in the postnatal period and a major peak in young age, starting at puberty? And, paradoxically, small risk in old age, although spermatogenesis is a lifelong process? Why is this type of cancer more common in individuals with maldeveloped gonads, including undescended testis, gonadal dysgenesis and androgen insensitivity syndrome? Why has there, during the past 50 years, been a quite dramatic increase in testicular cancer in many developed countries? These are just a few of many questions concerning testicular cancer. However, the recent progress in research in the early stages of testicular cancer (carcinoma in situ testis (CIS)) allows us to begin to answer some of these questions. There is more and more evidence that the CIS cell is a gonocyte with stem cell potential, which explains why an adult man can develop a non-seminoma, which is a neoplastic caricature of embryonic growth. We consider the possibility that CIS cells may loose their stem cell potential with ageing. Along these lines, a seminoma is regarded a gonocytoma where the single gonocytes have little or no stem cell potential. The Sertoli and Leydig cells, which are activated postnatally and during and after puberty, may play a crucial role for both the development of the CIS gonocyte and progression of the neoplasm to invasiveness. The reported increase in testicular cancer is not the only sign that male reproductive health is at risk. There are reports that undescended testis and hypospadias have become more common. Also semen quality has deteriorated, at least in some countries. The epidemiological evidence suggests that environmental factors may play a role. Are the environmental hormone disrupters (e.g. DDT, PCB, nonylphenol, bisphenol A) to be blamed for the apparently synchronised deterioration in these aspects of male reproductive health?     

Coalescence Index of Protein-Stabilized Emulsions

A simple method is proposed to estimate coalescence stability of protein-stabilized emulsions. Coalescence was accelerated through agitation and measured by change in emulsion turbidity over time. A coalescence index (CI) was determined and used to compare emulsions stabilized with casein, whey (WPI) and soy protein isolates (SPI). CI increased when stirring rate increased. Casein produced more stable emulsions, followed by WPI and SPI. High homogenization pressure increased coalescence stability of WPI and SPI-stabilized emulsions and decreased coalescence stability of casein-stabilized emulsions. Microscopic examination, showed agitation of the emulsion had clearly induced formation of large oil droplets which acted as coalescence nuclei.     

Production of tubular structures from the aerial mycelium of Actinomyces roseoflavus var. roseofungini]

Jejunal lamina propria plasma cells and eosinophils and intraepithelial lymphocytes were raised in coeliac children on gluten-containing diets, but only intraepithelial lymphocytes were increased in patients on gluten-free diets. In contrast, lamina propria lymphocytes were reduced in children with coeliad disease on gluten-containing diets but were normal in paitents on gluten-free diets. In children with coeliac disease who were studied serially, lamina propria plasma cells and eosinophils and intraepithelial lymphocytes increased, and lamina propria lymphocytes decreased, within three months of the reintroduction of gluten to the diet. These observations are essentially similar to those made in the adult form of the disease and suggest that more than one type of immunological reaction is involved in the pathogenesis of the jejunal lesion.